Physical squeeze can cause stem cells to grow and divide faster

A new study by scientists from the United States has shown that physically squeezing cells, can significantly accelerate their growth and division. Researchers at the Massachusetts Institute of Technology (MIT) and Boston Children’s Hospital have found that physical crowding at the cellular level increases the likelihood of interactions that can significantly alter cell health and development.

At first glance, trying to accelerate growth by squeezing may seem counterintuitive. However, the research team believes that this pushes the water out of the cell and concentrates its contents. And when certain proteins are in close proximity, they can trigger signaling and activate genes.

In a new study, published in the journal Cell Stem Cell, scientists have shown that compressioning gut cells triggers clusters of proteins along a specific signaling pathway that helps cells maintain an undifferentiated stem state that allows them to rapidly grow and differentiate into specialized cells.

Ming Guo, an assistant professor at the MIT, says that if cells can be simply squeezed to promote their “stemness”, they can be directed to create miniature organs such as artificial intestines, which will then be used as platforms to study functions, test new drugs, and even as transplants for regenerative medicine.

To study the effect of squeezing on cells, the researchers mixed different types of cells in solutions that solidified as rubbery slabs of hydrogel. To compress the cells, they placed weights on the hydrogel’s surface, in the form of either a quarter or a dime.

“We wanted to achieve a significant amount of cell size change, and those two weights can compress the cell by something like 10 to 30 percent of their total volume”, – said Ming Guo.

The team used a confocal microscope to measure in 3D the shape modification of individual cells as each sample was compressed. As they expected, the cells shrank with pressure. But did the compression affect their internal organization?

To answer this question, the researchers first tested the change in cell water content. The team concluded that external pressure pushes water out of the cell, making it less hydrated and, as a result, more rigid.

Scientists measured cell stiffness before and after exposure to loads using optical tweezers, a laser device that Guo’s lab has used for years to study interactions within cells. They found that the cells did become stiff under pressure. In addition, the contents of the compressed cells were less mobile, suggesting that they were compressed in comparison with the normal state.

Next, the scientists tested for changes in the interactions between certain proteins in cells in response to contraction. They focused on several proteins that are known to trigger Wnt/β-catenin signaling, which is involved in cell growth and stem cell maintenance.

“In general, this pathway is known to make a cell more like a stem cell“, – Guo says. “If you change this pathway’s activity, how cancer progresses and how embryos develop have been shown to be very different. So we thought we could use this pathway to demonstrate how cell crowding is important.”

To test whether cell shrinkage affects the Wnt pathway and cell growth rate, the researchers grew small organelles – miniature organs that are clusters of cells harvested from the intestines of mice.

“The Wnt pathway is particularly important in the colon”, – Guo says, pointing out that the cells that line the human intestine are constantly being replenished. The Wnt pathway, he says, is essential for maintaining intestinal stem cells, generating new cells, and “refreshing” the intestinal lining.

Guo and his colleagues grew intestinal organelles about half a millimeter in size in several Petri dishes, and then “squeezed” them by soaking the dishes with polymers. In organelles immersed in polymer, osmotic pressure increased and displaced water from their cells.

Guo’s team noticed that as a result, specific proteins involved in the activation of the Wnt pathway were packed closer together and were more likely to group together to turn on the pathway and activate its growth-regulating genes.

The results showed that those organelles that underwent compression grew noticeably faster and larger, with more stem cells on their surface, than those that grew under normal conditions.

“The difference was very obvious”, – Guo says. “Whenever you apply pressure, the organoids grow even bigger, with a lot more stem cells.”

The results also showed that cell behavior can change depending on the amount of water it contains.

“This is very general and broad, and the potential impact is profound, that cells can simply tune how much water they have to tune their biological consequences”, – Guo says.

Going forward, he and his colleagues plan to study cell squeezing as a way to accelerate the growth of artificial organs that scientists can use to test new, personalized drugs.